Oxytocin and dementia: beyond social and affection, the hormone that unhinge amyloid toxicity

Alzheimer’s disease is a progressive disorder in which the nerve cells (neurons) in a person’s brain and the connections among them degenerate slowly, causing severe memory loss, intellectual deficiencies, and deterioration in motor skills and communication.

One of the main causes of Alzheimer’s is the accumulation of a protein called amyloid β (Aβ) in clusters around neurons in the brain, which hampers their activity and triggers their degeneration. Studies in animal models have found that increasing the aggregation of Aβ in the hippocampus–the brain’s main learning and memory center–causes a decline in the signal transmission potential of the neurons therein. This degeneration affects a specific trait of the neurons, called “synaptic plasticity,” which is the ability of synapses (the site of signal exchange between neurons) to adapt to an increase or decrease in signaling activity over time. Synaptic plasticity is crucial to the development of learning and cognitive functions in the hippocampus. Thus, Aβ and its role in causing cognitive memory and deficits have been the focus of most research aimed at finding treatments for Alzheimer’s.

Now, advancing this research effort, a team of scientists from Japan, led by Professor Akiyoshi Saitoh from the Tokyo University of Science, has looked at oxytocin, a hormone conventionally known for its role in the female reproductive system and in inducing the feelings of love and well-being. Oxytocin was recently found to be involved in regulating learning and memory performance, but so far, no previous study deals with the effect of oxytocin on Aβ-induced cognitive impairment. Realizing this, Prof Saitoh’s group set out to connect the dots. Their findings are published in Biochemical and Biophysical Research Communication. Prof Saitoh and team first perfused slices of the mouse hippocampus with Aβ to confirm that Aβ causes the signaling abilities of neurons in the slices to decline or–in other words–impairs their synaptic plasticity. Upon additional perfusion with oxytocin, however, the signaling abilities increased, suggesting that oxytocin can reverse the impairment of synaptic plasticity that Aβ causes. To find out how oxytocin achieves this, they conducted a further series of experiments.

In a normal brain, oxytocin acts by binding with special structures in the membranes of brain cells, called oxytocin receptors. The scientists artificially “blocked” these receptors in the mouse hippocampus slices to see if oxytocin could reverse Aβ-induced impairment of synaptic plasticity without binding to these receptors. Expectedly, when oxytocin receptors were blocked, oxytocin could not reverse the effect of Aβ, which shows that these receptors are essential for oxytocin to act. Oxytocin is known to facilitate certain cellular chemical activities that are important in neuronal signaling involved in socialization, affection and memory, such as influx of calcium ions. Previous studies have suspected that Aβ suppresses some of these chemical activities. When the scientists artificially blocked these chemical activities, they found that addition of oxytocin addition to the hippocampal slices did not reverse the damage to synaptic plasticity caused by Aβ. Additionally, they found that oxytocin itself does not have any effect on synaptic plasticity in the hippocampus, but it is somehow able to reverse the toxic effects of Aβ.

Some effects of oxytocin were also indirect, since its signaling recruited a form of glutamate receptor called AMPA. Indeed, most of the cellear effects seen were abrogated by the AMPA antagonist NASPM. Prof Saitoh explained: “This is the first study in the world that has shown that oxytocin can reverse Aβ-induced impairments in the mouse hippocampus. This is only a first step and further research remains to be conducted in vivo in animal models and then humans before sufficient knowledge can be gathered to reposition oxytocin into a drug for Alzheimer’s. At present, there are no sufficiently satisfactory drugs to treat dementia, and new therapies with novel mechanisms of action are desired. Our study puts forth the interesting possibility that oxytocin could be a novel therapeutic modality for the treatment of memory loss associated with cognitive disorders such as Alzheimer’s disease. We expect that our findings will open up a new pathway to the creation of new drugs for the treatment of dementia caused by Alzheimer’s disease”.

  • Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.

Scientific references

Takahashia J et al. Biochem Biophys Res Commun 2020 Jul 12.

Inoue T, Yamakage H et al. Cells. 2019 May 31; 8(6):527.

Finger E et al. Alzheimers Res Ther. 2018 Sep 27; 10(1):102.

0 0 vote
Article Rating
Informazioni su Dott. Gianfrancesco Cormaci 2450 Articoli
- Laurea in Medicina e Chirurgia nel 1998 (MD Degree in 1998) - Specialista in Biochimica Clinica nel 2002 (Clinical Biochemistry specialty in 2002) - Dottorato in Neurobiologia nel 2006 (Neurobiology PhD in 2006) - Ha soggiornato negli Stati Uniti, Baltimora (MD) come ricercatore alle dipendenze del National Institute on Drug Abuse (NIDA/NIH) e poi alla Johns Hopkins University, dal 2004 al 2008. - Dal 2009 si occupa di Medicina personalizzata. - Detentore di un brevetto sulla preparazione di prodotti gluten-free a partire da regolare farina di frumento immunologicamente neutralizzata (owner of a patent concerning the production of bakery gluten-free products, starting from regular wheat flour). - Responsabile del reparto Ricerca e Sviluppo per la società CoFood s.r.l. (leader of the R&D for the partnership CoFood s.r.l.) - Autore di un libro riguardante la salute e l'alimentazione, con approfondimenti su come questa condizioni tutti i sistemi corporei. - Autore di articoli su informazione medica, salute e benessere sui siti web salutesicilia.com e medicomunicare.it
Subscribe
Notificami

Questo sito usa Akismet per ridurre lo spam. Scopri come i tuoi dati vengono elaborati.

0 Commenti
Inline Feedbacks
View all comments